547046
research-article2014
IJSXXX10.1177/1066896914547046International Journal of Surgical PathologyYegen et al
Case Report
Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract: A Case Report and Review of the Literature
International Journal of Surgical Pathology 2015, Vol. 23(1) 61–67 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914547046 ijs.sagepub.com
Gülçin Yegen, MD1, Mine Güllüoğlu, MD1, Özgür Mete, MD2, Semen Önder, MD1, and Yersu Kapran, MD1
Abstract Clear cell sarcoma is a rare tumor classically associated with tendons and aponeuroses of lower extremities of young adults and has a distinctive histopathologic and molecular profile. It has been rarely described in other locations other than soft tissues, including the gastrointestinal tract. Herein we report a case of clear cell sarcoma of gastrointestinal tract arising in the ileum, which is rich in osteoclast-like giant cells with a review of the literature. Keywords clear cell sarcoma, gastrointestinal tract, immunohistochemistry, fluorescence in situ hybridization (FISH)
Introduction Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, was first described by Enzinger in 1965 and is classically associated with tendons and aponeuroses of lower extremities of young adults.1,2 Besides sharing the same immunohistochemical profile and ultrastructural features with malignant melanoma, CCS is also genetically distinct as it lacks BRAF mutations and shows a recurrent chromosomal translocation t(12;22)(q13;q12), resulting in the fusion of the EWS gene on 22q12 with the ATF-1 gene on 12q13.3-10 Deep soft tissues of the lower extremities close to tendons and aponeuoroses are the principle site of involvement.1,2,4,7 However, rare examples in other locations, including the ear, penis, retroperitoneum, mediastinum, bone, and visceral organs have been described.3,4,10-12 CCS primarily arising in the gastrointestinal tract is extremely rare. To date, 42 cases of gastrointestinal CCS with or without genetic confirmation have been reported.3,4,11,13-30,32-35 In this study, we report a case of CCS of gastrointestinal tract with discussion on diagnostic difficulties and the review of literature.
Clinical History A 25-year-old woman presented with pallor and was found to have iron-deficiency anemia. Abdominal ultrasonography showed multiple hypoechoic nodules at the right and left lobes of the liver with maximum diameter of 5 cm and a hyperechoic cystic lesion of 4 cm at left ovary. A computed tomography scan revealed a segmental thickening of
the distal jejunum and proximal ileum with adjacent mesenteric lymphadenopathy and multiple nodules in the liver. Following a computed tomography–guided core biopsy from liver lesions and fine-needle aspiration biopsy (FNAB) from the intestinal tumor site, partial resection of small bowel, measuring 8.7 cm in length, and resection of liver metastases were performed.
Materials and Methods Cell block of FNAB, liver core biopsy, and the resection specimen were fixed in neutral, phosphate-buffered, 10% formalin, and routinely processed with tissue sections embedded in paraffin and stained with hematoxylin and eosin. Immunohistochemical studies were performed on representative sections of the tumor. Prediluated antibodies were used for S100 protein, vimentin, bcl-1, β-catenin, AE1/AE3, CD117, CD34, smooth muscle actin (SMA), desmin, chromogranin A, synaptophysin, CD10, HMB45, melan-A for both liver core biopsy–cell block and resection specimen. Also antibodies for p16 and EMA for resection specimen and CD56 for liver core biopsy–cell block were performed. The reaction product was detected with 3,3-diaminobenzidine chromogen.
1
Istanbul University, Istanbul, Turkey University of Toronto, Toronto, Ontario, Canada
2
Corresponding Author: Gülçin Yegen, Department of Pathology, Istanbul Medical Faculty, Istanbul University, Şehremini, Istanbul 34000, Turkey. Email: [email protected]
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Figure 1. Microscopic sections of the cell block of fine-needle aspiration biopsy (A) and liver core biopsy (B) showed a tumor with pseudopapillary pattern. Tumor cells were polygonal with a clear to eosinophilic cytoplasm, and oval to round, often vesicular nuclei with a single prominent nucleolus.
Paraffin-embedded sections were used for interphase fluorescence in situ hybridization (FISH) analysis. The commercially available breakapart EWSR1 probeset (Abbott) was used.
Results Microscopic sections of the liver core biopsy and the cell block of FNAB showed a tumor with pseudopapillary pattern. Tumor cells were polygonal with a clear to eosinophilic cytoplasm, and oval to round, often vesicular nuclei with a single prominent nucleolus. Pseudopapillary pattern was particularly striking, mimicking an epithelial neoplasm with papillary architecture or pancreatic solid pseudopapillary tumor (Figure 1A and B). The tumor was immunoreactive for S100 protein, vimentin, CD56, bcl-1 and β-catenin; negative for AE1/ AE3, CD117, CD34, SMA, desmin, chromogranin A, synaptophysin, CD10, HMB-45, and melan-A. It was reported as “malignant tumor with pseudopapillary pattern” and total excision was recommended. Grossly, resected segment of ileum showed, superficially ulcerated, circumferential tumor, gray-white in color, measuring 3.2 cm in diameter, involving the entire thickness of the intestinal wall and extending into the subserosa (Figure 2). Dissected lymph nodes were free of tumor. Cut surface of the liver metastasectomy specimens showed gray-white, focally hemorrhagic, solid lesions with a maximum diameter of 7 cm (Figure 3). On microscopic examination, tumor was found to be centered in the muscular layer of the intestine, invading the mucosa and subserosa (Figure 4A). The tumor cells were arranged in alveolar, solid, and focally pseudopapillary pattern. The cells were polygonal with a clear to
Figure 2. Resected segment of ileum showed superficially ulcerated, circumferential tumor, gray-white in color, measuring 3.2 cm in diameter.
Figure 3. Cut surface of the liver metastasectomy specimens showed gray-white, focally hemorrhagic, solid lesions with a maximum diameter of 7 cm.
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Figure 4. Low-power view of the tumor. The tumor is mainly localized in the muscular layer of the intestine (A). The tumor cells were arranged in an alveolar, solid pattern. The cells were polygonal with a clear to eosinophilic cytoplasm. The nuclei were oval, often vesicular with a single prominent nucleolus. Scattered multinucleated, osteoclast type giant cells were identified as well (B).
eosinophilic cytoplasm. The nuclei were oval, often vesicular with a single prominent nucleolus. Scattered multinucleated, osteoclast-type giant cells were identified as well (Figure 4B). Tumor cells were strongly immunoreactive for S100 protein (Figure 5), vimentin, and focally for bcl-1, p16, and β-catenin. AE1/AE3, EMA, CD117, CD34, SMA, desmin, chromogranin A, synaptophysin, CD10, HMB-45, and melan-A were all negative. Ki-67 score was 35%. The microscopic appearance and the immunohistochemical profile of the metastatic liver lesions were identical to those of the primary tumor. The resection margins were free of disease. Fluorescence in situ hybridization analysis detected rearrangement of EWSR1 gene in 84% of the cells, which is consistent with the diagnosis of CCS. With these findings, diagnosis of metastatic CCS of the gastrointestinal tractus became definite. Postoperative chemotherapy was administered. Fifteen months after the initial diagnosis metastatic lesions measuring 0.7 cm and 0.8 cm was detected in the liver. On her last follow-up at 47 months, bilateral ovarian and widespread peritoneal metastasis were detected and confirmed by pathologic evaluation.
Discussion Clear cell sarcoma is a relatively rare tumor that most commonly affects young adults with a peak incidence in the third and fourth decades.2 Deep soft tissues of the lower extremities close to tendons and aponeuroses are the principal sites of involvement.2,4,7 However, very rare examples at visceral locations have been described.3,4,10-12
Figure 5. Strong nuclear and cytoplasmic S100 protein immunoreactivity.
Up to now, 43 cases of CCS of the digestive tract have been reported (including our case). Clinicopathological features of those cases and present case are summarized in Table 1. There is no sex predilection and the median age is 37 years (range = 10-85 years). The most common site appears to be small bowel, in particular, the ileum. Median tumor size is 4.25 cm (range = 1.5-13.5 cm). The majority of the tumors are described as ulcerated masses involving all the layers of the intestinal or gastric wall. About half of the cases have regional lymph node metastasis at the time of diagnosis. Besides lymph nodes, liver seems to be the most common metastatic site. Intraperitoneal spread,
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International Journal of Surgical Pathology 23(1)
Table 1. Review of Reported Clear Cell Sarcoma Cases of Gastrointestinal Tract.
Reference
Age (Years)/ Gender
Site
11
38/Male
Duodenum
13
37/Male
Ileum
3
74/Male
4
Osteoclast-Type Size (cm) Giant Cells
Molecular Confirmation
Positive Immunohistochemical Results
3
−
No
S100 protein, HMB45(f)
6,5
−
S100 protein, vimentin
2
−
30/Male
Transverse colon Stomach
4
−
14
15/Female
Jejunum
5
+
Yes Karyotype analysis Yes RT-PCR Yes Karyotype analysis, FISH Yes Karyotype analysis
14
21/Female
Jejunum
4
+
No
S100 protein, vimentin
14
35/Female
Ileum
3,5
+
No
S100 protein, vimentin
14 14
37/Female 13/Male
Ileum Stomach
4,5 6,7
+ +
No No
S100 protein, vimentin S100 protein, vimentin
14 15
32/Male 57/Male
Ileum Jejunum
5 6,5
+ −
16
35/Male
Ileum
1,8
−
No Yes FISH Yes RT-PCR
S100 protein, vimentin S100 protein, HMB45, melan-A, tyrosinase S100 protein, melan-A, tyrosinase
17
21/Female
Ileum
7
−
S100 protein, vimentin
18
41/Male
Jejunum
8,7
+
Yes FISH Yes FISH
21
85/Femalea
Ileum
NR
−
21
47/Female
Pankreas
NR
−
19 22
40/Male 81/Female
Stomach Ascending colon
3 NR
+ −
22
42/Female
Ileum
NR
+
Yes FISH, RT-PCRb
22
42/Female
Ileum
3,7
−
Yes RT-PCRb
22
51/Female
Ileum
2,8
NR
22
18/Female
NR
NR
23
31/Female
Small bowel Ileum
2,8
−
25
46/Male
Jejunum
11
−
25
62/Male
Ileum
4
−
25
48/Male
Ceacum
10,5
−
Yes RT-PCR, FISH Yes RT-PCR, FISH No Yes FISH, RT-PCRb
Yes FISH Yes RT-PCR Yes FISH Yes RT-PCR, FISH Yes RT-PCR, FISH Yes RT-PCR(+)
S100 protein, HMB45, vimentin S100 protein, vimentin, CD99, NSE S100 protein, vimentin
S100 protein, vimentin, β-catenin, bcl-2, PDGF receptor-α S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A S100 protein, vimentin S100 protein, Vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE S100 protein, vimentin, NSE S100 protein, vimentin S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A
Regional or Metastatic Spread/ Outcome LN mets and spread to pancreas at diagnosis/NED at 18 months Liver mets after 24 and 46 months/AWD at 46 months Liver mets after 9 months/ NED at 15 months Regional LN and peritoneal mets at diagnosis Mesenteric LN mets at diagnosis/ DOD 16 at months Liver and LN mets at diagnosis/ DOD at 12 months LN at diagnosis and liver mets after 12 months NR —/Local recurrence after 29 months LN mets at diagnosis NR Liver mets after 2 months, peritoneal mets after 7 months/DOD at 15 months LN mets at diagnosis Liver mets after 6 months
LN mets at diagnosis/DOD at 1 month NED at 24 months LN mets at diagnosis LN mets at diagnosis, liver mets after 5 years —
Peritoneal and liver mets at diagnosis Liver and peritoneal mets at 5 years/AWD Local recurrence LN mets at diagnosis NED at 7 months Mediastinal LN, lung mets at diagnosis/DOD at 12 months LN mets at diagnosis, CNS mets after 1.5 month/DOD at 2 months (continued)
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Yegen et al Table 1. (continued)
Reference
Age (Years)/ Gender
Site
Osteoclast-Type Size (cm) Giant Cells
Molecular Confirmation
25
60/Male
Jejunum
10
−
Yes PCR, FISH
5
37/Male
Jejunum
8,2
−
Yes FISH
24
20?/Female
Ileum
3
+
6
60/Male
Ileum
2.4
+
Yes RT-PCR Yes FISH
6
46/Male
Jejunum
6
−
20
10/Female
Stomach
7,8
−
24
Ileum
3
+
29
Early 20s/ Female 15/Male
Ileum
NR
NR
27
16/Male
Ileum
5
+
28
53/Female
Ileum
5
+
Yes RT-PCR, FISH
28
26/Female
13,5/10,1
−
Yes FISH, RT-PCRb
28
66/Male
Small and large bowel Ileum
2,5
−
32
69/Female
Ileum
5,9
+
33
15/Male
Ileum
4
NR
34
36/Female
Jejunum
1,5
+
Yes FISH, RT-PCRb Yes FISH Yes FISH Yes FISH
36
49/Female
Jejunum
3
NR
PC
25/Female
Ileum
3,2
+
FISH negative for EWSR1 rearrangement Yes Karyotype analysis, RT-PCR, FISH Yes RT-PCR Yes FISH Yes Karyotype analysis, RT-PCR
Yes FISH Yes FISH
Positive Immunohistochemical Results
Regional or Metastatic Spread/ Outcome
S100 protein, HMB45, melan-A
LN mets at diagnosis, intraabdominal mets after 12 month/DOD at 28 months Peritoneal extension and S100 protein, HMB45, pleural effusion after 2 E-cadherin, β-catenin, PDGF-receptor-α, bcl-2, months p53, vimentin(f), p16, EMA S100 protein — S100 protein, CD56(f), synaptophysin(f), vimentin(f) S100 protein, CD56(f), vimentin(f)
LN and liver mets at diagnosis
S100 protein, vimentin
LN and liver mets at diagnosis/ NED at 4 months
S100 protein
NED at 24 months
NR
NR
S100 protein, EMA (f)
Multiple mesenteric and omentum mets and lung nodule at 2 weeks/DOD at 1 month Regional LN mets at diagnosis/ NED at 7 months
S100 protein(f), vimentin, AE1/3(f), CD57(f), bcl2(f) S100 protein, EMA (f)
LN and liver mets at diagnosis
Lost to follow-up
S100 protein
Regional LN mets at diagnosis/ NED S100 protein, CD56, INI 1 Liver met at 6 months/AWD S100 protein, vimentin
Liver met at 12 months
S100 protein, bcl2, CD57, NR EMA (f), CD56 (f), AE1AE3(f) S100 protein, EMA (f) NED at 20 months S100 protein, vimentin, β-catenin, P16
Liver mets at diagnosis and at 15 months. Ovarian mets and peritoneal dissemination at 47 months
Abbreviations: f, focal; mets, metastases; LN, lymph node; FISH, fluorescence in situ hybridization; RT-PCR, reverse transcription polymerase chain reaction; NR, not reported; NED, no evidence of disease; AWD, alive with disease; DOD, dead of disease; PC, present case. a Cases with previous history of malignant melanoma. b Genetical confirmation for EWS-CREB1.
mediastinal lymph node and lung metastasis have been reported in a few cases as well. To our knowldge our case is the first case metastasing to the ovary. The clinical behavior of gastrointestinal tract CCS appears more aggressive than its soft tissue counterpart, as 20.6% (7 of
34) patient with molecular confirmation is dead from disease, generally
research-article2014
IJSXXX10.1177/1066896914547046International Journal of Surgical PathologyYegen et al
Case Report
Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract: A Case Report and Review of the Literature
International Journal of Surgical Pathology 2015, Vol. 23(1) 61–67 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914547046 ijs.sagepub.com
Gülçin Yegen, MD1, Mine Güllüoğlu, MD1, Özgür Mete, MD2, Semen Önder, MD1, and Yersu Kapran, MD1
Abstract Clear cell sarcoma is a rare tumor classically associated with tendons and aponeuroses of lower extremities of young adults and has a distinctive histopathologic and molecular profile. It has been rarely described in other locations other than soft tissues, including the gastrointestinal tract. Herein we report a case of clear cell sarcoma of gastrointestinal tract arising in the ileum, which is rich in osteoclast-like giant cells with a review of the literature. Keywords clear cell sarcoma, gastrointestinal tract, immunohistochemistry, fluorescence in situ hybridization (FISH)
Introduction Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, was first described by Enzinger in 1965 and is classically associated with tendons and aponeuroses of lower extremities of young adults.1,2 Besides sharing the same immunohistochemical profile and ultrastructural features with malignant melanoma, CCS is also genetically distinct as it lacks BRAF mutations and shows a recurrent chromosomal translocation t(12;22)(q13;q12), resulting in the fusion of the EWS gene on 22q12 with the ATF-1 gene on 12q13.3-10 Deep soft tissues of the lower extremities close to tendons and aponeuoroses are the principle site of involvement.1,2,4,7 However, rare examples in other locations, including the ear, penis, retroperitoneum, mediastinum, bone, and visceral organs have been described.3,4,10-12 CCS primarily arising in the gastrointestinal tract is extremely rare. To date, 42 cases of gastrointestinal CCS with or without genetic confirmation have been reported.3,4,11,13-30,32-35 In this study, we report a case of CCS of gastrointestinal tract with discussion on diagnostic difficulties and the review of literature.
Clinical History A 25-year-old woman presented with pallor and was found to have iron-deficiency anemia. Abdominal ultrasonography showed multiple hypoechoic nodules at the right and left lobes of the liver with maximum diameter of 5 cm and a hyperechoic cystic lesion of 4 cm at left ovary. A computed tomography scan revealed a segmental thickening of
the distal jejunum and proximal ileum with adjacent mesenteric lymphadenopathy and multiple nodules in the liver. Following a computed tomography–guided core biopsy from liver lesions and fine-needle aspiration biopsy (FNAB) from the intestinal tumor site, partial resection of small bowel, measuring 8.7 cm in length, and resection of liver metastases were performed.
Materials and Methods Cell block of FNAB, liver core biopsy, and the resection specimen were fixed in neutral, phosphate-buffered, 10% formalin, and routinely processed with tissue sections embedded in paraffin and stained with hematoxylin and eosin. Immunohistochemical studies were performed on representative sections of the tumor. Prediluated antibodies were used for S100 protein, vimentin, bcl-1, β-catenin, AE1/AE3, CD117, CD34, smooth muscle actin (SMA), desmin, chromogranin A, synaptophysin, CD10, HMB45, melan-A for both liver core biopsy–cell block and resection specimen. Also antibodies for p16 and EMA for resection specimen and CD56 for liver core biopsy–cell block were performed. The reaction product was detected with 3,3-diaminobenzidine chromogen.
1
Istanbul University, Istanbul, Turkey University of Toronto, Toronto, Ontario, Canada
2
Corresponding Author: Gülçin Yegen, Department of Pathology, Istanbul Medical Faculty, Istanbul University, Şehremini, Istanbul 34000, Turkey. Email: [email protected]
Downloaded from ijs.sagepub.com at UQ Library on March 15, 2015
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International Journal of Surgical Pathology 23(1)
Figure 1. Microscopic sections of the cell block of fine-needle aspiration biopsy (A) and liver core biopsy (B) showed a tumor with pseudopapillary pattern. Tumor cells were polygonal with a clear to eosinophilic cytoplasm, and oval to round, often vesicular nuclei with a single prominent nucleolus.
Paraffin-embedded sections were used for interphase fluorescence in situ hybridization (FISH) analysis. The commercially available breakapart EWSR1 probeset (Abbott) was used.
Results Microscopic sections of the liver core biopsy and the cell block of FNAB showed a tumor with pseudopapillary pattern. Tumor cells were polygonal with a clear to eosinophilic cytoplasm, and oval to round, often vesicular nuclei with a single prominent nucleolus. Pseudopapillary pattern was particularly striking, mimicking an epithelial neoplasm with papillary architecture or pancreatic solid pseudopapillary tumor (Figure 1A and B). The tumor was immunoreactive for S100 protein, vimentin, CD56, bcl-1 and β-catenin; negative for AE1/ AE3, CD117, CD34, SMA, desmin, chromogranin A, synaptophysin, CD10, HMB-45, and melan-A. It was reported as “malignant tumor with pseudopapillary pattern” and total excision was recommended. Grossly, resected segment of ileum showed, superficially ulcerated, circumferential tumor, gray-white in color, measuring 3.2 cm in diameter, involving the entire thickness of the intestinal wall and extending into the subserosa (Figure 2). Dissected lymph nodes were free of tumor. Cut surface of the liver metastasectomy specimens showed gray-white, focally hemorrhagic, solid lesions with a maximum diameter of 7 cm (Figure 3). On microscopic examination, tumor was found to be centered in the muscular layer of the intestine, invading the mucosa and subserosa (Figure 4A). The tumor cells were arranged in alveolar, solid, and focally pseudopapillary pattern. The cells were polygonal with a clear to
Figure 2. Resected segment of ileum showed superficially ulcerated, circumferential tumor, gray-white in color, measuring 3.2 cm in diameter.
Figure 3. Cut surface of the liver metastasectomy specimens showed gray-white, focally hemorrhagic, solid lesions with a maximum diameter of 7 cm.
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Yegen et al
Figure 4. Low-power view of the tumor. The tumor is mainly localized in the muscular layer of the intestine (A). The tumor cells were arranged in an alveolar, solid pattern. The cells were polygonal with a clear to eosinophilic cytoplasm. The nuclei were oval, often vesicular with a single prominent nucleolus. Scattered multinucleated, osteoclast type giant cells were identified as well (B).
eosinophilic cytoplasm. The nuclei were oval, often vesicular with a single prominent nucleolus. Scattered multinucleated, osteoclast-type giant cells were identified as well (Figure 4B). Tumor cells were strongly immunoreactive for S100 protein (Figure 5), vimentin, and focally for bcl-1, p16, and β-catenin. AE1/AE3, EMA, CD117, CD34, SMA, desmin, chromogranin A, synaptophysin, CD10, HMB-45, and melan-A were all negative. Ki-67 score was 35%. The microscopic appearance and the immunohistochemical profile of the metastatic liver lesions were identical to those of the primary tumor. The resection margins were free of disease. Fluorescence in situ hybridization analysis detected rearrangement of EWSR1 gene in 84% of the cells, which is consistent with the diagnosis of CCS. With these findings, diagnosis of metastatic CCS of the gastrointestinal tractus became definite. Postoperative chemotherapy was administered. Fifteen months after the initial diagnosis metastatic lesions measuring 0.7 cm and 0.8 cm was detected in the liver. On her last follow-up at 47 months, bilateral ovarian and widespread peritoneal metastasis were detected and confirmed by pathologic evaluation.
Discussion Clear cell sarcoma is a relatively rare tumor that most commonly affects young adults with a peak incidence in the third and fourth decades.2 Deep soft tissues of the lower extremities close to tendons and aponeuroses are the principal sites of involvement.2,4,7 However, very rare examples at visceral locations have been described.3,4,10-12
Figure 5. Strong nuclear and cytoplasmic S100 protein immunoreactivity.
Up to now, 43 cases of CCS of the digestive tract have been reported (including our case). Clinicopathological features of those cases and present case are summarized in Table 1. There is no sex predilection and the median age is 37 years (range = 10-85 years). The most common site appears to be small bowel, in particular, the ileum. Median tumor size is 4.25 cm (range = 1.5-13.5 cm). The majority of the tumors are described as ulcerated masses involving all the layers of the intestinal or gastric wall. About half of the cases have regional lymph node metastasis at the time of diagnosis. Besides lymph nodes, liver seems to be the most common metastatic site. Intraperitoneal spread,
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International Journal of Surgical Pathology 23(1)
Table 1. Review of Reported Clear Cell Sarcoma Cases of Gastrointestinal Tract.
Reference
Age (Years)/ Gender
Site
11
38/Male
Duodenum
13
37/Male
Ileum
3
74/Male
4
Osteoclast-Type Size (cm) Giant Cells
Molecular Confirmation
Positive Immunohistochemical Results
3
−
No
S100 protein, HMB45(f)
6,5
−
S100 protein, vimentin
2
−
30/Male
Transverse colon Stomach
4
−
14
15/Female
Jejunum
5
+
Yes Karyotype analysis Yes RT-PCR Yes Karyotype analysis, FISH Yes Karyotype analysis
14
21/Female
Jejunum
4
+
No
S100 protein, vimentin
14
35/Female
Ileum
3,5
+
No
S100 protein, vimentin
14 14
37/Female 13/Male
Ileum Stomach
4,5 6,7
+ +
No No
S100 protein, vimentin S100 protein, vimentin
14 15
32/Male 57/Male
Ileum Jejunum
5 6,5
+ −
16
35/Male
Ileum
1,8
−
No Yes FISH Yes RT-PCR
S100 protein, vimentin S100 protein, HMB45, melan-A, tyrosinase S100 protein, melan-A, tyrosinase
17
21/Female
Ileum
7
−
S100 protein, vimentin
18
41/Male
Jejunum
8,7
+
Yes FISH Yes FISH
21
85/Femalea
Ileum
NR
−
21
47/Female
Pankreas
NR
−
19 22
40/Male 81/Female
Stomach Ascending colon
3 NR
+ −
22
42/Female
Ileum
NR
+
Yes FISH, RT-PCRb
22
42/Female
Ileum
3,7
−
Yes RT-PCRb
22
51/Female
Ileum
2,8
NR
22
18/Female
NR
NR
23
31/Female
Small bowel Ileum
2,8
−
25
46/Male
Jejunum
11
−
25
62/Male
Ileum
4
−
25
48/Male
Ceacum
10,5
−
Yes RT-PCR, FISH Yes RT-PCR, FISH No Yes FISH, RT-PCRb
Yes FISH Yes RT-PCR Yes FISH Yes RT-PCR, FISH Yes RT-PCR, FISH Yes RT-PCR(+)
S100 protein, HMB45, vimentin S100 protein, vimentin, CD99, NSE S100 protein, vimentin
S100 protein, vimentin, β-catenin, bcl-2, PDGF receptor-α S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A S100 protein, vimentin S100 protein, Vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE, CD56, synaptophysin S100 protein, vimentin, NSE S100 protein, vimentin, NSE S100 protein, vimentin S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A S100 protein, HMB45, melan-A
Regional or Metastatic Spread/ Outcome LN mets and spread to pancreas at diagnosis/NED at 18 months Liver mets after 24 and 46 months/AWD at 46 months Liver mets after 9 months/ NED at 15 months Regional LN and peritoneal mets at diagnosis Mesenteric LN mets at diagnosis/ DOD 16 at months Liver and LN mets at diagnosis/ DOD at 12 months LN at diagnosis and liver mets after 12 months NR —/Local recurrence after 29 months LN mets at diagnosis NR Liver mets after 2 months, peritoneal mets after 7 months/DOD at 15 months LN mets at diagnosis Liver mets after 6 months
LN mets at diagnosis/DOD at 1 month NED at 24 months LN mets at diagnosis LN mets at diagnosis, liver mets after 5 years —
Peritoneal and liver mets at diagnosis Liver and peritoneal mets at 5 years/AWD Local recurrence LN mets at diagnosis NED at 7 months Mediastinal LN, lung mets at diagnosis/DOD at 12 months LN mets at diagnosis, CNS mets after 1.5 month/DOD at 2 months (continued)
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Yegen et al Table 1. (continued)
Reference
Age (Years)/ Gender
Site
Osteoclast-Type Size (cm) Giant Cells
Molecular Confirmation
25
60/Male
Jejunum
10
−
Yes PCR, FISH
5
37/Male
Jejunum
8,2
−
Yes FISH
24
20?/Female
Ileum
3
+
6
60/Male
Ileum
2.4
+
Yes RT-PCR Yes FISH
6
46/Male
Jejunum
6
−
20
10/Female
Stomach
7,8
−
24
Ileum
3
+
29
Early 20s/ Female 15/Male
Ileum
NR
NR
27
16/Male
Ileum
5
+
28
53/Female
Ileum
5
+
Yes RT-PCR, FISH
28
26/Female
13,5/10,1
−
Yes FISH, RT-PCRb
28
66/Male
Small and large bowel Ileum
2,5
−
32
69/Female
Ileum
5,9
+
33
15/Male
Ileum
4
NR
34
36/Female
Jejunum
1,5
+
Yes FISH, RT-PCRb Yes FISH Yes FISH Yes FISH
36
49/Female
Jejunum
3
NR
PC
25/Female
Ileum
3,2
+
FISH negative for EWSR1 rearrangement Yes Karyotype analysis, RT-PCR, FISH Yes RT-PCR Yes FISH Yes Karyotype analysis, RT-PCR
Yes FISH Yes FISH
Positive Immunohistochemical Results
Regional or Metastatic Spread/ Outcome
S100 protein, HMB45, melan-A
LN mets at diagnosis, intraabdominal mets after 12 month/DOD at 28 months Peritoneal extension and S100 protein, HMB45, pleural effusion after 2 E-cadherin, β-catenin, PDGF-receptor-α, bcl-2, months p53, vimentin(f), p16, EMA S100 protein — S100 protein, CD56(f), synaptophysin(f), vimentin(f) S100 protein, CD56(f), vimentin(f)
LN and liver mets at diagnosis
S100 protein, vimentin
LN and liver mets at diagnosis/ NED at 4 months
S100 protein
NED at 24 months
NR
NR
S100 protein, EMA (f)
Multiple mesenteric and omentum mets and lung nodule at 2 weeks/DOD at 1 month Regional LN mets at diagnosis/ NED at 7 months
S100 protein(f), vimentin, AE1/3(f), CD57(f), bcl2(f) S100 protein, EMA (f)
LN and liver mets at diagnosis
Lost to follow-up
S100 protein
Regional LN mets at diagnosis/ NED S100 protein, CD56, INI 1 Liver met at 6 months/AWD S100 protein, vimentin
Liver met at 12 months
S100 protein, bcl2, CD57, NR EMA (f), CD56 (f), AE1AE3(f) S100 protein, EMA (f) NED at 20 months S100 protein, vimentin, β-catenin, P16
Liver mets at diagnosis and at 15 months. Ovarian mets and peritoneal dissemination at 47 months
Abbreviations: f, focal; mets, metastases; LN, lymph node; FISH, fluorescence in situ hybridization; RT-PCR, reverse transcription polymerase chain reaction; NR, not reported; NED, no evidence of disease; AWD, alive with disease; DOD, dead of disease; PC, present case. a Cases with previous history of malignant melanoma. b Genetical confirmation for EWS-CREB1.
mediastinal lymph node and lung metastasis have been reported in a few cases as well. To our knowldge our case is the first case metastasing to the ovary. The clinical behavior of gastrointestinal tract CCS appears more aggressive than its soft tissue counterpart, as 20.6% (7 of
34) patient with molecular confirmation is dead from disease, generally
